Ciprofloxacin

Key points

• The boxed warning reserves ciprofloxacin for patients who have no alternative treatment option for three ordinary infections: acute exacerbation of chronic bronchitis, acute uncomplicated cystitis and acute sinusitis.
• Ciprofloxacin inhibits the human cytochrome P450 1A2 pathway, so co-administered drugs cleared mainly by CYP1A2 reach higher plasma concentrations.
• The serum elimination half-life is approximately 4 hours in people with normal renal function.
• In a paediatric trial, musculoskeletal adverse reactions affected 9.3% of ciprofloxacin-treated patients against 6% on comparators within six weeks, and 13.7% against 9.5% by one year.

How it works

The UK summary of product characteristics states that ciprofloxacin’s bactericidal action results from inhibiting two bacterial enzymes, type II topoisomerase (DNA-gyrase) and topoisomerase IV, which bacteria need for DNA replication, transcription, repair and recombination. The same document notes that resistance to ciprofloxacin can be acquired in a stepwise way through target-site mutations in both of those enzymes.

Safety specific to ciprofloxacin

The boxed warning on the oral tablet label has three parts, and all three bear on whether the medicine is the right choice.

First, fluoroquinolones including ciprofloxacin have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together in the same patient: tendinitis and tendon rupture, peripheral neuropathy, and central nervous system effects. Two words in that sentence carry most of its weight. The harm may not reverse, and these reactions can arrive as a group rather than one at a time.

Second, the warning instructs that ciprofloxacin be discontinued immediately, and fluoroquinolones avoided, in any patient who experiences one of those reactions. It adds that fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis, and that ciprofloxacin should be avoided in anyone with a known history of that condition.

Third, because of those reactions, the warning reserves ciprofloxacin for patients who have no alternative treatment options for acute exacerbation of chronic bronchitis, acute uncomplicated cystitis and acute sinusitis. Those are the everyday infections this antibiotic is most associated with, and the label’s position is that it should not be the first answer to any of them.

Two further warnings sit outside the box. Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. Separately, Clostridioides difficile-associated diarrhoea has been reported with use of nearly all antibacterial agents, including ciprofloxacin, and may range in severity from mild diarrhoea to fatal colitis.

When to seek urgent care

The label directs that ciprofloxacin be discontinued immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity. Tendon pain or swelling, new numbness or tingling, and changes in mood, memory or perception are the reactions the boxed warning asks both patient and prescriber to act on rather than wait out.

Further reading

• CIPROFLOXACIN tablet, film coated
• Ciprofloxacin 500mg film-coated tablets